The effect of dietary Coriolus versicolor supplementation at 0%, 0.01%, 0.1%, and 1.0% on the hematology and innate immune response of olive flounder (Paralichthys olivaceus) against the ciliate Pseudocohnilembus persalinus was studied after one, two, and four weeks of feeding. White blood cells were significantly higher in fish fed the 0.1% and 1.0% diets than in those fed the control and 0.01% diets from week two onwards. Similarly, red blood cells were significantly higher in the 0.1% and 1.0% diets than the other diets at week 4. Hemoglobin was significantly highest in the 1.0% diet and hematocrit significantly highest in the 0.1% diet at weeks 2 and 4. Total protein, glucose, and calcium were significantly higher in fish fed the 0.1% and 1.0% supplementation diets from weeks 1 to 4. Scuticocidal and lysozyme activity were significantly enhanced in fish fed the 0.1% and 1.0% diets from week 1 to 4 while respiratory burst activity was significantly higher in fish fed the 0.1% and 1.0% diets from week 2 to 4. Cumulative mortality was lower in groups fed the 0.1% and 1.0% diets than in groups fed the control or 0.01% diets. The present study suggests that dietary supplementation with 0.1% or 1.0% C. versicolor protects hematological parameters, improves innate immune response, and affords protection from P. persalinus infection in olive flounder.